TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

doi:10.1038/cr.2016.93

	TALEN-based generation of a cynomolgus monkey disease model for human microcephaly
	Ke, Qiong 1,2,3,4; Li, Weiqiang 1,2,4,5; Lai, Xingqiang 2; Chen, Hong 2; Huang, Lihua 1; Kang, Zhuang 6; Li, Kai 7; Ren, Jie 7; Lin, Xiaofeng 8; Zheng, Haiqing 9; Huang, Weijun 2; Ma, Yunhan 10; Xu, Dongdong 10; Chen, Zheng 11; Song, Xinming 11; Lin, Xinyi 11; Zhuang, Min12 ; Wang, Tao 2,5; Zhuang, Fengfeng 13; Xi, Jianzhong 14; Mao, Frank Fuxiang 15; Xia, Huimin 1; Lahn, Bruce T.16; Zhou, Qi 17; Yang, Shihua 10; Xiang, Andy Peng 1,2,4,5
	2016-09
发表期刊	CELL RESEARCH
ISSN	1001-0602
卷号	26 期号:9 页码:1048-1061
发表状态	已发表
DOI	10.1038/cr.2016.93
摘要	Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size.
关键词	MCPH1 microcephaly TALEN gene mutant cynomolgus monkey
收录类别	SCI ; CSCD
语种	英语
资助项目	Pearl River S&T Nova Program of Guangzhou[2014J2200037]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000382398100010
CSCD记录号	CSCD:5803261
出版者	INST BIOCHEMISTRY & CELL BIOLOGY
WOS关键词	PREMATURE CHROMOSOME CONDENSATION ; HUMAN BRAIN SIZE ; MOUSE MODEL ; MCPH1 GENE ; MUTATION ; PRIMATE ; RHESUS ; CELLS ; TELOMERASE ; CHECKPOINT
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1732
专题	生命科学与技术学院_PI研究组_庄敏组
通讯作者	Zhou, Qi; Yang, Shihua; Xiang, Andy Peng
作者单位	1.Sun Yat Sen Univ, Affiliated Guangzhou Women & Childrens Hosp, Zhongshan Sch Med, Program Stem Cells & Regenerat Med, Guangzhou 510623, Guangdong, Peoples R China 2.Sun Yat Sen Univ, Ctr Stem Cell Biol & Tissue Engn, Key Lab Stem Cells & Tissue Engn, Minist Educ, Guangzhou 510080, Guangdong, Peoples R China 3.Sun Yat Sen Univ, Zhongshan Med Sch, Dept Biol, Guangzhou 510080, Guangdong, Peoples R China 4.Guangdong Key Lab Reprod Med, Guangzhou 510080, Guangdong, Peoples R China 5.Sun Yat Sen Univ, Zhongshan Med Sch, Dept Biochem, Guangzhou 510080, Guangdong, Peoples R China 6.Sun Yat Sen Univ, Dept Radiol, Affiliated Hosp 3, Guangzhou 510632, Guangdong, Peoples R China 7.Sun Yat Sen Univ, Dept Ultrasound, Affiliated Hosp 3, Guangzhou 510632, Guangdong, Peoples R China 8.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Radiol, Guangzhou 510120, Guangdong, Peoples R China 9.Sun Yat Sen Univ, Dept Rehabil Med Sci, Affiliated Hosp 3, Guangzhou 510632, Guangdong, Peoples R China 10.South China Agr Univ, Guangdong Prov Key Lab Prevent & Control Severe C, Coll Vet Med, Guangzhou 510642, Guangdong, Peoples R China 11.Sun Yat Sen Univ, Zhongshan Sch Med, Dept Med Genet, Guangzhou 510080, Guangdong, Peoples R China 12.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 13.Beijing ViewSolid Biotechnol, Beijing 100034, Peoples R China 14.Peking Univ, Coll Engn, Dept Biomed Engn, Yannan Yuan 60, Beijing 100871, Peoples R China 15.Sun Yat Sen Univ, Zhong Shan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China 16.Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA 17.Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China
推荐引用方式 GB/T 7714	Ke, Qiong,Li, Weiqiang,Lai, Xingqiang,et al. TALEN-based generation of a cynomolgus monkey disease model for human microcephaly[J]. CELL RESEARCH,2016,26(9):1048-1061.
APA	Ke, Qiong.,Li, Weiqiang.,Lai, Xingqiang.,Chen, Hong.,Huang, Lihua.,...&Xiang, Andy Peng.(2016).TALEN-based generation of a cynomolgus monkey disease model for human microcephaly.CELL RESEARCH,26(9),1048-1061.
MLA	Ke, Qiong,et al."TALEN-based generation of a cynomolgus monkey disease model for human microcephaly".CELL RESEARCH 26.9(2016):1048-1061.